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Type: Journal article
Title: The anti-diabetic drug metformin does not affect bone mass in vivo or fracture healing
Author: Jeyabalan, J.
Viollet, B.
Smitham, P.
Ellis, S.
Zaman, G.
Bardin, C.
Goodship, A.
Roux, J.
Pierre, M.
Chenu, C.
Citation: Osteoporosis International, 2013; 24(10):2659-2670
Publisher: Springer
Issue Date: 2013
ISSN: 0937-941X
Statement of
J. Jeyabalan, B. Viollet, P. Smitham, S.A. Ellis, G. Zaman, C. Bardin, A. Goodship, J.P. Roux, M. Pierre, C. Chenu
Abstract: Summary: The present study shows no adverse effects of the anti-diabetic drug metformin on bone mass and fracture healing in rodents but demonstrates that metformin is not osteogenic in vivo, as previously proposed. Introduction: In view of the increased incidence of fractures in patients with type 2 diabetes mellitus (T2DM), we investigated the effects of metformin, a widely used T2DM therapy, on bone mass and fracture healing in vivo using two different rodent models and modes of metformin administration. Methods: We first subjected 12-week-old female C57BL/6 mice to ovariectomy (OVX). Four weeks after OVX, mice received either saline or metformin administered by gavage (100 mg/kg/daily). After 4 weeks of treatment, bone micro-architecture and cellular activity were determined in tibia by micro-CT and bone histomorphometry. In another experiment, female Wistar rats aged 3 months were given only water or metformin for 8 weeks via the drinking water (2 mg/ml). After 4 weeks of treatment, a mid-diaphyseal osteotomy was performed in the left femur. Rats were sacrificed 4 weeks after osteotomy and bone architecture analysed by micro-CT in the right tibia while fracture healing and callus volume were determined in the left femur by X-ray analysis and micro-CT, respectively. Results: In both models, our results show no significant differences in cortical and trabecular bone architecture in metformin-treated rodents compared to saline. Metformin had no effect on bone resorption but reduced bone formation rate in trabecular bone. Mean X-ray scores assessed on control and metformin fractures showed no significant differences of healing between the groups. Fracture callus volume and mineral content after 4 weeks were similar in both groups. Conclusions: Our results indicate that metformin has no effect on bone mass in vivo or fracture healing in rodents.
Keywords: Bone architecture; fracture healing; histomorphometry; metformin; micro-CT
Rights: © The Author(s) 2013. This article is published with open access at
RMID: 0030042607
DOI: 10.1007/s00198-013-2371-0
Appears in Collections:Medicine publications

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